Because controlled studies characterizing immunological events that occur during the development of neoplasia have not been feasible in humans, attention has focussed on animal models to make such investigations possible. Practical use of such models has been predicated on the approximation both morphologically and pathogenetically of lesions of the same organ in man. One such agent N-(4-(5-nitro--2-furyl)-2-thiazolyl) formamide (FANFT), has been found in rats to induce in a predictable fashion bladder cancers that fulfill these necessary conditions. Its use, therefore, in the proposed study of lymphocyte and macrophage function and modulation in an animal model of bladder cancer seems highly indicated. The major objectives of the present study would be to characterize lymphocyte subpopulations and macrophages found directly in bladder cancer tissue, regional lymph nodes, and peripheral blood during different stages of cancer development in the FANFT model. Surface markers of purified lymphocyte subpopulations from each site would be determined by rosetting patterns with a variety of erythrocyte preparations and specific immunofluorescent staining characteristics. Cytotoxic mechanisms of these cells, separated on specifically prepared gels or glass beads according to cell-surface characteristics, would be examined using syngeneic and allogenic normal and neoplastic target cells in a 51Chromium-release assay. Finally, because previous work in our laboratory has demonstrated a possible participation of cyclic AMP in the modulation of the immune response to bladder cancer, the role of this substance in interactions between lymphocyte subpopulations or macrophages and tumor target cells during the development of bladder cancer in this model would be examined.